Diabetic retinopathy (DR) is the leading cause of blindness in the United States. The disorder is characterized by aberrant neovascularization ultimately leading to blindness. Currently, there is no drug treatment for DR patients and pannretinal laser coagulation surgery is the only option to delay blindness. Somatostinergic drugs are growth factor inhibitors that offer the potential to treat a probable cause of diabetic retinopathy by blocking key mediating steps in disease progression. Clinical trials with somatostatin peptide drugs in DR patients indicate that somatostatinergic drug therapy can stop neovascularization and improve visual acuity. However, the clinical results have been highly variable and have been best for patients receiving high dosage regimens or continuous parenteral treatment. These results are consistent with an inadequate blood-retinal barrier penetration of somatostatin peptide drugs to reach target retinal tissues. New non-peptide lipophilic somatostatin receptor agonists described herein have the potential to effectively penetrate the BRB. Using pharmacological in vitro and animal testing models of DR this study aims to establish structure activity relationships for this innovative class of compounds. The final goal is to identify a small potent somatostinergic molecule that readily accesses target retinal tissue for clinical testing in DR patients.